Trial Title:
Value of [68Ga]Ga-PSMA-11 PET/MRI in the Assessment of Liver Cirrhosis
NCT ID:
NCT06265272
Condition:
Liver Cirrhosis
Hepatic Cell Carcinoma
Portal Hypertension
Conditions: Official terms:
Carcinoma, Hepatocellular
Liver Cirrhosis
Hypertension, Portal
Fibrosis
Conditions: Keywords:
PET/MR
Cirrhosis
HCC
PSMA
68Ga PSMA
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Drug
Intervention name:
Injection of a gadolinium contrast agen
Description:
All patients will be requested to have an injection of a gadolinium contrast agent, which
may be either Gadavist (Bayer, Whippany, NJ, USA), Eovist (Bayer, Whippany, NJ, USA), or
Dotarem (Guerbet, Princeton, NJ, USA) (ancillary drugs).
- About halfway through the examination, the same intravenous catheter used to inject
the radiotracer will be used to inject the MRI contrast agent;
- After being positioned on the PET/MRI table, the nuclear medicine technicians will
connect the patient to the MRI-safe power-injector; - The catheter will be flushed
before and after injection with 0.9% saline solution;
Arm group label:
Cirrhosis
Intervention type:
Drug
Intervention name:
Radiotracer Injection
Description:
All patients will be requested to have a radiotracer injection of Ga-PSMA (Illucix, Telix
Pharmaceuticals). An intravenous catheter will be placed in an arm or hand vein for
injection of the Ga-PSMA;
- The catheter will be flushed post-injection with 0.9% saline solution
- The injected dose and the time of injection will be recorded.
- The subjects will be positioned on the scanner table; support devices under the back
and/or legs will be used to enable the patient to comfortably maintain his/her
position throughout the scan
Arm group label:
Cirrhosis
Intervention type:
Diagnostic Test
Intervention name:
Imaging
Description:
PET, MRI and fused PET/MRI images will be qualitatively assessed in comparison to
standard of reference data. For PET, standard of reference will be PET images as obtained
by standard PET acquisition mode. Attenuation correction of the PET images will be
performed using a 2-point Dixon MRI sequence and a vendor-specific atlas-based
attenuation map. 3D scatter correction by single scatter simulation is also performed
using the MRI-derived attenuation data. MRI images will be compared to dedicated 3 Tesla
MR upper abdominal protocol images acquired at the MGH in patients with liver cirrhosis,
including those undergoing imaging follow-up after systemic or local regional therapies.
For PET/MRI fused images, the standard of reference will be co-registered and fused
PET/MRI images as obtained by standard MRI sequences/reconstructions.
Arm group label:
Cirrhosis
Summary:
A total of fifty-five (55) patients with liver cirrhosis will be enrolled in this study
to produce and validate dedicated Ga-PSMA-PET/MRI acquisition protocols.
The specific hypotheses include:
- Ga-PSMA PET/MRI may allow robust and reproducible noninvasive in vivo quantitation
of hepatic macro and microhemodynamics in cirrhotic patients
- Dedicated simultaneously acquired DWI sequences might quantitate liver fibrosis and
improve hemodynamic quantitation.
- Ga-PSMA PET/MRI may allow noninvasive and reproducible quantitation of portal venous
hypertension and predict its evolution, as well as response to treatments
- Ga-PSMA PET/MRI may improve noninvasive and reproducible qualitative and
quantitative assessment of liver function, structure, nodules and predict evolution
of cirrhosis
Detailed description:
[68Ga]Ga-PSMA-11(Ga-PSMA) is a novel radiotracer approved by the FDA in late 2020 to
investigate prostate cancer in men. This compound targets the prostate-specific membrane
antigen, which unlike the name suggests, has been detected in other anatomical regions,
mainly associated with neoangiogenesis. The high affinity of PSMA toward neoangiogenesis
can play several roles in imaging liver cirrhosis. In particular, it may highlight
neovasculature and help distinguish microhemodynamic changes caused by shunting from
those caused by increased vascular permeability associated to neoangiogenesis. Thus,
Ga-PSMA may improve the interpretation of MRp maps, of DWI data (which is also influenced
by microperfusion) and might add more confidence on Li-Rad classifications.
For each candidate patient subject, the study staff will first contact the treating
clinician to inquire as to their willingness to allow investigators to approach the
subject to participate in this study. The clinician will initially introduce the study to
the patient and will obtain the patient's permission to be contacted by the study staff.
One of the investigators or other study staff will then approach the subjects in
accordance with PHRC policy. At the time of initial discussions about potentially
participating in this study, the investigators will make it clear to potential subjects
that the study scan is performed at the Charlestown Navy Yard to allow them to decide if
travel associated with participation is too inconvenient. Subjects will be informed that
a decision to participate or not in the PET/MRI protocol will not affect their care
within MGH or any other Mass General Brigham facility. Informed consent will be obtained
from the subjects by licensed physician principal investigator, licensed physician
co-investigator, or licensed nurse practitioners listed as co-investigators with backup
from a licensed physician investigator listed on study staff.
PET/MRI images will be acquired using the Biograph mMR combined 3 Tesla PET/MRI scanner.
The image quality on these 3 Tesla devices will be very high, typical, or better than any
other standard clinical MRI system. Subjects will be asked to lie still for the duration
of the study. The investigators expect the entire imaging session to last about 80
minutes and not to exceed 120 minutes.
The investigators will be comparing:
1. Different sequences, acquisition protocols and reconstruction modeling in term of
image quality, reduction of artifacts, improved signal and contrast to noise ratios,
reproducibility of the quantitative features.
2. PSMA-PET/MRI quantitative and qualitative features, including hybrid biomarkers
obtained incorporating PSMA uptake with MRp and/or 4D-MRI and/or DWI extracted
parameters, with clinical data that provide insights into liver function and liver
hemodynamics
3. PSMA-PET/MRI qualitative and quantitative features (for example vascular
permeability or median velocity), including hybrid biomarkers, with clinical data to
explore possibility of assessing liver function, quantify fibrosis, facilitate
Li-Rad classification, measure hemodynamics in cirrhotic patients including those
treated/ to be treated for portal hypertension.
4. Comparison of fused Ga-PSMA PET/MRI images with stand-alone MRI images and
stand-alone PET images obtained in the same scan in terms of qualitative and
quantitative imaging features, for example confidence in characterization of
band-like fibrosis or differentiation of mild from moderate degree of fibrosis.
5. The investigators will also follow up patients to ascertain if Ga-PSMA PET/MRI
result might have impacted on clinical management.
Descriptive statistics will be used to compare the performance (detection rates,
sensitivity, and specificity) of PET/MRI and MRI alone. When calculating sensitivity and
specificity for each imaging modality, the gold standard will be considered whole-liver
pathology for patients who undergo liver transplant; or biopsy/surgical pathology results
in patients that do not undergo liver transplantation but are directed to biopsy; or
finally imaging follow-up in patients who undergo follow-up only. No biopsy or image
follow-up will be ever ordered for the sake of this study. They will be ordered only for
standard clinical care. Means and standard deviations or median and (IQR) will be
reported for continuous variables according to the variable distributions. Categorical
variables will be reported as counts and proportions, and 95% Confidence Intervals will
be included when applicable. A p-value <0.05 will be considered statistically
significant. For the primary endpoint analysis, confusion matrices will be constructed
comparing PET/MRI to PET alone ant to MRI alone. Each lesion described by the readers of
the imaging modalities will then be classified accordingly into true positive, false
positive, true negative or false negative. Sensitivity, specificity, accuracy, positive
predictive value, and negative predictive value will then be computed using the adequate
proportions as estimates. Additional parameters that will be evaluated include region of
interest location, size, apparent diffusion coefficient value, and standardized uptake
value, and quantitative MRp metrics.
Criteria for eligibility:
Study pop:
Fifty-five subjects will be recruited. All subjects recruited for the study will be able
to withdraw from the study at any time.
Healthy Volunteers: The investigators will not be recruiting or enrolling healthy
volunteers in this study. Patients with liver cirrhosis: Fifty-five (55)
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- Liver cirrhosis as diagnosed by imaging and/or clinical data, including pathology
Exclusion Criteria:
- Any contraindication to PET, as in attached screening form
- Any contraindication to MRI, as in attached screening form
- Any contraindication to gadolinium-based contrast agent, including allergy to
gadolinium, as in attached screening forms.
- Pregnancy
- Breast feeding.
- Cumulative radiation exposure for research studies during the prior 12 months,
combined with the exposure from this study, > 50 mSv
- Inability to fit in the scanner: weight > 300 lbs or BMI > 33
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Address:
City:
Charlestown
Zip:
02129
Country:
United States
Status:
Recruiting
Contact:
Last name:
Onforio Catalano, MD, Ph.D
Phone:
617-724-4030
Email:
ocatalano@mgh.harvard.edu
Contact backup:
Last name:
Diandrea Galloway
Phone:
617-643-1407
Email:
dgalloway@mgh.harvard.edu
Start date:
December 10, 2023
Completion date:
December 19, 2026
Lead sponsor:
Agency:
Massachusetts General Hospital
Agency class:
Other
Source:
Massachusetts General Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06265272
https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer
http://illuccixhcp.com/wp-content/uploads/illuccix-prescribing-information.pdf
